Abstract: Objective To prepare an irritable bowel syndrome with diarrhea ( IBS-D) mouse model by rectal perfusion with acetic acid combined with restraint stress, and to evaluate the feasibility of the model. Methods Forty-five male C57BL/ 6J mice were divided into a healthy control group (Group C), 3% acetic acid group (Group A), and 3% acetic acid combined with restraint stress group (Group A+R). The body weights and survival rates of the groups were compared before and after intervention, and the fecal water content, total intestinal transport time, and colonic pain threshold of each group were compared after intervention. The advantages and disadvantages of the two modeling method were then assessed. Pathological changes to the colons in Group C and Group A + R were observed. Fluorescein isothiocyanate-dextran 4 (FD4) was used to evaluate the integrity of the intestinal mucosa of mice in Group C, and the model with the best success rate was determined. To clarify the pathological characteristics of this modeling method, the serum contents of 5-HT and TNF-α were determined by ELISA, and the expression of 5-HTR3A in colon tissue was detected with immunohistochemistry. Results Compared with Group C, Group A+R had a significantly increased colonic pain threshold and fecal water content (P< 0.001). The total intestinal transport time was significantly shortened (P< 0.05), and the colonic pain threshold and fecal water content were significantly decreased in Group A ( P< 0.005); however, there was no significant difference in intestinal transport time between the groups (P> 0.05). Compared with Group C, Group A+C showed a significant increase in the content of plasma FD4 and serum 5-HT and TNF-α and the expression of 5-HTR3A in colon tissues (P< 0.05). Conclusions Compared with 3% acetic acid, treatment with 3% acetic acid combined with restraint stress more convincingly simulated the local intestinal symptoms and related pathological changes seen in IBS-D patients.

Abstract: Objective To construct a humanized-immune-system mouse model with human pancreatic cancer and evaluate its effectiveness in order to provide an ideal preclinical animal model for pancreatic cancer immunotherapy research. Methods Ficoll density gradient centrifugation was used to isolate fresh peripheral blood mononuclear cells (PBMC) from healthy people. The cells were injected into the tail vein of severe combined immunodeficiency NOD/ ShiltJ- Prkdc em26Cd52 Il2rg em26Cd22 ( NCG) mice to construct a model with a humanized immune system. We then subcutaneously implanted human pancreatic cancer Aspc1 cells into the mice and regularly monitored tumor growth. Three weeks later, the peripheral blood of the reconstructed mice was collected for flow cytometric analysis to detect the levels of human CD45⁺ cells. When the tumors grew to 100 ~ 200 mm³ , immunotherapy with human anti-PD-1 monoclonal antibody was started. After continuous treatment for 3 weeks, the mice were euthanized, and samples taken. Flow cytometry, immunohistochemistry, and other method were used to analyze the infiltration and activation of human immune cells in the peripheral blood, spleen, bone marrow, and tumor tissues of the humanized-immune-system mice with human pancreatic cancer. Results Three weeks after implantation of human PBMC, high levels of human CD45⁺ cells were detected in the peripheral blood, spleen, and bone marrow of the mice. The reconstructed humanized immune system inhibited the growth of human tumors (P< 0.01, P< 0.001) and was activated by human anti-PD-1 monoclonal antibody to promote cytotoxic CD8⁺ T cell infiltration and PD-L1 expression in the tumor tissues. Conclusions A humanized immune system mouse model with human pancreatic cancer was successfully constructed. The reconstructed humanized immune system responded well to human anti-PD-1 monoclonal antibodies and restrained the growth of human pancreatic tumor cells. Thus, this study has provided an ideal preclinical animal model of immunotherapy for pancreatic cancer.

Abstract: Objective To investigate the protective effects of Dahuang Mudan against liver injury in rats with acute pancreatitis. Methods Overall, 96 SPF Wistar rats were randomly divided into blank, model, Dahuang Mudan decoction high-, medium-, and low-dose (14, 7, 3. 5 g / (kg·d), respectively), and octreotide (10 μg / ( kg·d)) groups, with 16 animals in each group. The acute pancreatitis model was generated by retrograde injection of 5% sodium taurocholate solution into the pancreaticobiliary duct. before the model and every 12 h after the model. Samples were collected 24 h after the mold. To observe the rats’ general physical signs, serum amylase (AMS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (ChE), and C-reactive protein (CRP) contents were biochemically determined, and hematoxylin and eosin staining used to observe pancreatic and hepatic histopathological changes. ELISA was employed to detect rat liver tissue TNF-α, IL-1β, and IL-6 contents, and western blotting was used to detect the expression of key rat liver PI3K/ Akt pathway proteins. Results (1) Compared with the blank group, the model group rats’ general survival status was relatively poor; their contents of AMS, ALT, AST, and CRP increased and that of ChE decreased. Microscopic analysis of HE staining showed the pancreatic tissue had incomplete structure, and was necrotic and congested with severe inflammatory infiltration; liver cells showed disordered arrangement, and liver tissue showed necrosis, steatosis, and inflammatory infiltration. The TNF-α, IL-1β, and IL-6 contents of the liver tissue homogenate were significantly increased; PI3K, p-Akt, p-NF-κB p65, and Bax protein expression levels decreased and Bcl-2 protein expression increased, especially in the Dahuang Mudan high-dose group, and the difference was statistically significant ( P< 0. 05). ( 2) Compared with the model group, the general condition of the rats in each treatment group improved to varying degrees: the degree of pancreatic tissue edema, congestion, and necrosis visible under the microscope was significantly improved, and liver cell arrangement disorder, necrosis, steatosis, inflammatory infiltration, among others, were alleviated. AMS, ALT, AST, and CRP contents decreased to varying degrees, and the ChE content increased. Liver tissue homogenate TNF-α, IL- 1β, and IL-6 contents decreased; PI3K, p-Akt, p-NF-κB p65, and Bax protein levels decreased; while the levels of Bcl-2 protein increased, especially in the Dahuang Mudan high-dose group, and the differences were statistically significant (P< 0. 05). Conclusions Dahuang Mudan decoction effectively improved the general health, biochemical indicators, and pathological changes to the pancreas and liver of acute pancreatitis model rats. The mechanism of its liver-damage-reducing action may involve regulation of the PI3K/ Akt signaling pathway.

Abstract: Objective To establish an LCMV-CL13 chronic infection mouse model and analyze its use for B cell somatic hypermutation research. Methods C57BL/ 6N mice were inoculated with 2×10⁶ plaque-forming units of LCMV- CL13 virus via tail vein injection. The tissue viral load was then detected by quantitative polymerase chain reaction on days 10, 20, 30, 40, 50, 60, and 70 post-infection. The CD4⁺ and CD8⁺T cell and CD19⁺ B cell ratios in peripheral blood and the germinal center B cell percentage of the spleen were determined by flow cytometry, and the gene abundance and BCR V region mutation rate were analyzed using immune repertoire technology. Results LCMV-CL13-infected mice maintained a tissue viral load of 1×10⁶ copies/ μL virus. The percentage of CD4⁺ T cells in the peripheral blood gradually increased in the infection plateau phase to ( 13. 15% ± 0. 72%), while the percentage of CD8⁺ T cells first decreased to ( 2. 17% ± 0. 40%) and then gradually recovered to (6. 65% ± 0. 52%), and the percentages of CD19⁺ B cells and germinal center B cells increased to (40. 32% ± 0. 46%) and (10. 03% ± 0. 60%), respectively. Sequencing result demonstrated that the frequency of V gene usage decreased and the mutation rate of the heavy chain CDR3 V gene increased 1. 7-fold with increasing infection time. Conclusions We successfully established a LCMV-CL13 chronic infection mouse model. This model can be used to study BCR mutations, and provides a research tool for investigating B cell somatic hypermutation caused by chronic viral infection.

Abstract: Objective To establish an endothelial conditional EMCN-knockout mouse model and explore the differences between tumor lung metastases in these and C57BL/ 6 mice. Methods Endothelial-cell-specific Tek-creERT2 mice were mated with EMCN^{flox / flox} mice. Male EMCN^{flox / wt} / Tek-CreERT2⁺ mice were crossed with female EMCN^{flox / flox} mice to acquire endothelial cell-specific EMCN-knockout mice ( EMCN^{flox / flox} / Tek-CreERT2⁺ , EMCN^ecko ). To verify the gene knockout accuracy and efficiency at the DNA and protein level, the genomic DNA of mice was extracted, and the Tek- creERT2 and Flox sites were detected by PCR amplification. After tamoxifen induction, expression of the EMCN protein was detected on Western Blot. The phenotypes of normal C57BL/ 6 mice and EMCN^ecko mice were observed, and the organs were stained with hematoxylin and eosin ( HE). To confirm the effect of EMCN knockout on tumor metastasis, ( Lewis lung carcinoma, LLC) LLC cells were intravenously injected into C57BL/ 6 and EMCN^ecko mice. After 2 weeks, the lungs were dissected to detect metastasis, and the result for the two groups of mice were compared and analyzed. LLC cells were subcutaneously injected into C57BL/ 6 and EMCN^ecko mice. The subcutaneous tumors were removed 2 weeks later, and lung metastasis was observed 2 and 3 weeks after the operation. The lung tissues were stained with HE, and the metastasis result of the two groups were compared and analyzed. Results We confirmed the successful construction of EMCN^{flox / flox} / Tek- CreERT2⁺ mice at the gene and protein level. Preliminary phenotypic analysis showed no abnormal organ development in the gene-knockout mice. C57BL/ 6 and EMCN^ecko mice given intravenous injection and tumor resection after subcutaneous injection can develop lung metastases. Compared with C57BL/ 6 mice, the deletion of endothelial cell EMCN expression significantly promoted lung metastasis. Conclusions Endothelial-cell-specific EMCN-knockout mice were successfully obtained. The frequency of lung metastasis in endothelial cell EMCN-knockout mice was significantly higher than that in normal C57BL/ 6 mice. This approach is expected to provide an efficient lung metastasis animal model for the study of tumor metastasis .

Abstract: Objective To investigate the anti-inflammatory and antioxidant effects of liensinine ( LIE) derived from lotus on a lipopolysaccharide (LPS)-induced RAW264. 7 macrophage inflammatory model, and to study the molecular mechanisms responsible for these effects in relation to the nuclear factor ( NF-κB), mitogen-activated protein kinase (MAPK), and nuclear factor-erythroid factor 2-related factor 2 ( Nrf2) / heme oxygenase ( HO)-1 pathways. Methods RAW264. 7 macrophages were divided into Control group, LPS group and LIE ( 0. 5, 1, 2 μmol / L) groups. Cells were subjected to Cell Counting Kit 8 screening of non-cytotoxic concentrations of LIE, nitric oxide (NO) was detected by the Griess method, prostaglandin 2 (PGE2) and pro-inflammatory factors (TNF-α,IL-6 and IL-1β) were detected by enzyme- linked immunoassay, cyclooxygenase-2 ( COX-2) and inducible nitric oxide ( iNOS ) synthase gene expression were detected by real-time polymerase chain reaction, and reactive oxygen species (ROS) were detected by dichloro-dihydro- fluorescein diacetate assay ( which detects superoxide dismutase ( SOD ) activity and glutathione ( GSH ) and malondialdehyde (MDA) contents), and NF-κB, MAPK, and Nrf2 / HO-1 pathway protein expression were detected by Western Blot. Results LIE 0 ~ 4 μmol / L had no effect on cell viability. Levels of pro-inflammatory factors levels were significantly lower in the LIE (0. 5, 1, 2 μmol / L) group compared with the LPS group, NO and PGE2 concentrations and COX-2 and iNOS mRNA expression levels were all decreased, and NF-κB and MAPK pathways were inhibited ( P< 0.05) in dose-dependent manners. The ROS and MDA contents were also significantly lower and SOD activity and GSH were significantly higher compared with the LPS group (P< 0.01), and the activity of the Nrf2 / HO-1 pathway was also significantly higher than that of the LPS group (P< 0.05). Conclusions LIE exerts anti-inflammatory and antioxidant effects by inhibiting the NF-κB and MAPK pathways and activating the Nrf2 / HO-1 pathway.

Abstract: Objective To quickly evaluate the immune enhancement effect of Chinese herbal compound extract (CHCe) and study the potential mechanism using in vitro cell and in vivo zebrafish models. Methods In the in vitro experiments, RAW 264. 7 mouse mononuclear macrophage cells were treated with vinorelbine tartrate, and the protective effect of CHCe on vinorelbine tartrate-induced toxicity was evaluated. The zebrafish immunocompromised model was established using vinorelbine tartrate. The number of macrophages and their phagocytic function, the number of T- lymphocytes, and the expression of inflammation- and immune-related genes in zebrafish were used to observe the effects of CHCe in the zebrafish immunocompromised model. Results The result showed that CHCe had good biosafety and increased the survival rate of RAW 264. 7 cells treated with 250 μg / mL vinorelbine tartrate. In vivo studies showed that 222, 667 and 2000 μg / mL CHCe significantly inhibited the reduction of macrophages induced by vinorelbine and enhanced the phagocytic ability of macrophages. Both 222 and 667 μg / mL CHCe significantly increased the number of T- lymphocytes, and 222, 667 and 2000 μg / mL CHCe significantly restored the down-regulation of rag1 and rag2 genes in the model group, and down-regulated the expression of tumor necrosis factor-α. A dose of 222 μg / mL CHCe up-regulated the relative expression level of interleukin-12, and 2000 μg / mL CHCe up-regulated the relative expression level of interferon-γ. Conclusions In vivo and in vitro experiments showed that CHCe had a marked immunity enhancement effect.

Abstract: Objective To investigate the effects of curcumin and / or aerobic exercise on intestinal function in dyslipidemic rats. Methods Forty specific-pathogen free male Sprague Dawley rats were divided randomly into the following groups: normal diet + quiet (CON group), high-fat diet + quiet (HDC group), high-fat diet + curcumin + quiet (HDM group), high-fat diet + aerobic exercise (HDE group), and high-fat diet + curcumin + aerobic exercise (HDME group). All the high-fat diet groups received a high-fat diet and the CON group received a maintenance diet. From the third week, the HDM and HDME groups were also given 200 g / ( kg·d) curcumin, and the other groups were given 0. 5% sodium carboxymethyl cellulose. The HDE and HDME groups underwent aerobic exercise intervention with 70% ~ 75% maximal oxygen uptake, while the other groups did not undergo any exercise intervention. Twenty-four hours after the 6 weeks intervention, blood was taken from the abdominal aorta, and cecal tissue and contents were collected. Blood lipid levels were detected using an automatic biochemical analyzer. Cecal morphology was observed by hematoxylin and eosin staining. Expression of zonula occludens-1 (ZO-1) protein in cecal tissue was detected by western blot. The distribution of the intestinal flora in the cecal contents was detected by 16S rDNA sequencing. Results Curcumin and / or aerobic exercise significantly decreased serum total cholesterol and triglyceride levels (P< 0.05), up-regulated ZO-1 expression in cecal tissue ( P< 0.05), attenuated the cecal histopathological changes, and improved the diversity and evenness of the intestinal flora in dyslipidemic rats (P< 0.05). Conclusions Curcumin and / or aerobic exercise can reduce blood lipid levels in dyslipidemic rats, regulate the cecal intestinal flora, protect the integrity of the intestinal mucosal barrier, and adjust intestinal function, with the combination of curcumin and aerobic exercise having the greatest effect.

Abstract: Objective To construct a humanized chimeric mouse model by subcutaneously transplanting NOD- SCID immunodeficient mice with kidney-derived cells cultured from healthy human urine mixed with human mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells ( HUVECs). Methods ( 1) Kidney-derived cells were isolated from healthy human urine and cultured in vitro. MSCs and HUVECs were also cultured in vitro. All three kinds of cells were identified by immunofluorescence. (2)The three cell types were then mixed in a ratio of 3 ∶ 3 ∶ 2 and injected subcutaneously with Matrigel into NOD-SCID mice to develop human tissue. The transplantation model was identified by hematoxylin and eosin staining and immunohistochemistry. Results (1) Kidney-derived cells were successfully isolated and cultured from urine, and renal tubular epithelial cells and collecting duct cells were detectable and identified by immunohistochemistry. (2) After subcutaneous injection into NOD-SCID immunodeficient mice, the three kinds of cells initially developed tubule structures and human-derived vascular structures that communicated with the murine systemic circulation. Conclusions We successfully created a chimeric mouse model of the human renal vascular unit by subcutaneous transplantation of kidney-derived cells, HUVECs, and MSCs, including renal tubular epithelial cells and collecting tubular cells, into NOD-SCID immunodeficient mice. This model may provide a humanized animal model for research into the individualized treatment of human chronic kidney disease and kidney-related viral infections.

Abstract: Objective To establish a tree shrew model of H1N1 influenza virus infection and to explore the dynamics of the influenza virus and its distribution in respiratory tissues. Methods Twenty-four 3 to 3.5-years-old adult tree shrews (Tupaia Belangeri Chinensis), with equal numbers of males and females, were randomly divided into a blank group (group B) and a model group ( group M) of 12 tree shrews each. H1N1 influenza virus 600 μL/ bird (1 ×10^6.8 TCID50 / 0. 1 mL) were inoculated into M group tree shrews through the nasal cavity; the rectal temperature was measured every morning from rom 3 d before until 10 d after inoculation, and throat swabs, nasal swabs, and blood samples were collected to determine the viral load. Blood levels of neutralizing antibodies against influenza were determined on days 2, 4, and 7. Three tree shrews were randomly sacrificed on days 2, 3, 5,and 10, turbinate, trachea, pharynx, and lung tissues were collected for viral load detection, 3, 5, and 10 days of tissue were taken for histopathology. Results Tree shrews in group M showed clinical symptoms such as a disheveled coat, loss of appetite, slow movement, increased body temperature, and increased nasopharyngeal secretion, and their blood viral load appeared. There were some pathological changes to the turbinate, pharynx, trachea, and lung tissue of group M. Conclusions The clinical symptoms of tree shrews infected with influenza virus were very similar to those of humans. The established influenza virus tree shrew model provides a valuable tool for studying the pathogenesis of influenza and evaluating anti-influenza drugs.

Abstract: Objective To obtain a novel coronavirus pneumonia transgenic mouse model with constitutive human angiotensin converting enzyme 2 (hACE2) gene expression, that can efficiently maintain human physiological levels of a bacterial artificial chromosome ( BAC) hACE2 gene. This model could provide an important tool for research into cardiovascular disease, the pathogenesis of novel coronavirus pneumonia, and the development of drugs and vaccines. Methods A BAC plasmid containing the complete coding sequence of human ACE2 (hACE2) was purified and transgenic mice were established by fertilized egg microinjection and Fallopian tube transplantation. Stable F2 mouse strains were obtained by cross-breeding and analyzed in relation to integration of the hACE2 gene, gene copy number, relative fluorescence quantitative polymerase chain reaction (PCR), Western Blot, and immunofluorescence. Results Four mouse strains (hACE2-6-9, hACE2-14-3, hACE2-15-1 and hACE2-15-2) were obtained. The result of gene integration showed that the hACE2-6-9, hACE2-15-1 and hACE2-15-2 strains contained the complete hACE2 gene locus and long gene regulatory region, while hACE2-14-3 contained the complete hACE2 gene locus and a short gene regulatory 3' untranslated region. Relative fluorescence quantitative PCR and western blot showed that hACE2 mRNA and protein levels in the intestine were lower in the hACE2-6-9, hACE2-15-1 and hACE2-15-2 strains, while expression levels were higher in the hACE2-14-3 strain with shorter regulatory sequences. Immunofluorescence staining showed that hACE2 was expressed in renal tubular epithelial cells and pulmonary vascular endothelial cells in hACE2-15-1 mice. Conclusions We obtained novel coronavirus pneumonia hACE2 transgenic mice with the full-length gene sequence and the complete promoter and gene regulatory regions. This model will provide an important tool for the study of cardiovascular diseases and the pathogenesis of novel coronavirus pneumonia, as well as for examining mechanisms regulating hACE2 gene expression and the development of drugs and vaccines.

Abstract: Objective To isolate and culture primary small cell lung cancer ( SCLC) cells that retain the important characteristics and functions of the original tumor, and use them to construct a brain metastasis model of SCLC, as an animal model for drug development and the evaluation of patients with SCLC brain metastasis. Methods Fresh SCLC tumor tissue samples were collected from patients and transplanted subcutaneously into mice. The result ing patient-derived xenograft (PDX) mouse model of SCLC was assessed in terms of tumor presence, tumor size, and tumor growth. Primary cells were isolated and cultured from the tumor tissue after tumor formation, and their proliferation and invasion abilities were detected by cell scratch and proliferation tests. An SCLC brain metastasis model was constructed by injecting primary cells into the carotid artery, and the model was assessed in terms of its clinical manifestations and pathological observations. Results (1) A subcutaneous PDX model of SCLC was constructed successfully. The tumor passage time was about 56 days, and the tumor growth curve showed a logarithmic growth trend. (2)Primary L0 SCLC cells with tumorigenicity were successfully isolated and screened, and demonstrated strong cell migration and proliferation abilities. (3)An SCLC brain metastasis model was successfully constructed by carotid injection, and SCLC B0 cells with brain metastasis characteristics were isolated. Conclusions Primary SCLC cells were successfully isolated and cultured from SCLC tumor tissue samples, and a brain metastasis model using primary SCLC cells was successfully constructed.

Abstract: Objective To study the effects of compound microecological preparation on the immune function of the intestinal mucosa of mice. Methods BALB/ C mice at 28 days of age were selected for use in this study, and composite microecological preparations of high, medium, and low doses (2. 5, 5 and 10 g / kg body weight) were given by gavage. Blood and jejunum tissue were sampled on the 14th and 28th days, and the immune organ index was measured. The blood lysozyme content was detected by turbidimetry, and the jejunum mucosa SIgA and immune cytokine (IL-4, IL-10 and IFN- γ) contents of mice were detected by ELISA. The expression of immunocytokine mRNA in the jejunum mucosa was detected by fluorescence quantitative PCR. Results (1) The different compound microecological preparation doses increased the SIgA and immune cytokine contents and enhanced the expression of immune cytokine mRNA in the intestinal mucosa of mice. On the 14th day, the contents of IL-4, IL-10 and IFN-γ; the expression of IL-4, IL-10 and IFN-γ mRNA; and the content of SIgA were significantly higher in the treated groups than the control group (P < 0. 01). On the 28th day, the content of IL-4 in the jejunal mucosa of the low-dose and medium-dose groups was significantly increased (P< 0.01). In the middle-dose group, IL-10 and IFN-γ protein and mRNA levels and SIgA protein levels were significantly higher than those in the control group ( P< 0.01). In the middle-dose and high-dose groups, IL-4, IL-10, and IFN-γ mRNA expression was significantly higher than that in the control group ( P< 0.05 or P< 0.01). There was no significant difference in the expression of IL-4 and IL-10 mRNA between the low-dose and control groups (P> 0.05). (2)On the 14th day, the immune organ index of the medium dose group was significantly higher than that of the control group (P< 0.05). (3)On the 28th day, compared with the control group, each experimental group’ s immune organ index was significantly increased (P< 0.05). The lysozyme content of each experimental group was significantly higher than that of the control group (P< 0.05). Conclusions Compound microecological preparation promoted the growth and increased the immune organ index, lysozyme content, and intestinal mucosal immune function of mice, consequently reducing the incidence of intestinal infectious diseases.

Abstract: Objective To study the regulatory role of macrophage MED1 in the development of insulin resistance. Methods Eight-week-old and specific-pathogen-free male macrophage-specific MED1 knockout(MED1^ΔMac)and wild-type (MED1^{fl/ fl}) mice were used in this animal model study. Mice were fed a high-fat diet (HFD) for 0, 4, 8, 12, 16, 20 weeks to induce obesity and insulin resistance. Body weight, total triglyceride, total cholesterol and blood glucose were dynamically monitored every 4 weeks. Hematoxylin-eosin ( HE ) staining was used to observe liver and adipose histopathology after an HFD for 20 weeks. Results After an HFD regime, the body weight increase of MED1^ΔMac mice tended to be greater than that of the MED1^{fl/ fl} control group. The blood glucose of MED1^ΔMac mice increased significantly (P< 0. 01) compared with that of MED1^{fl/ fl} mice after an HFD for 20 weeks. Compared with the MED1^{fl/ fl} mice, the liver weight, subcutaneous fat weight and visceral fat weight of MED1^ΔMac mice also showed a tendency to increase. In addition, the hepatic steatosis was more severe in MED1^ΔMac mice than in MED1^{fl/ fl} mice. Furthermore, a glucose tolerance test (GTT) and insulin tolerance test (ITT) showed no significant difference in glucose tolerance or insulin sensitivity between the two groups. Conclusions Deficiency of macrophage MED1 promoted an increase in blood glucose levels but had no obvious effect on insulin resistance, suggesting macrophage MED1 has a key regulatory role in glucose metabolism.

Abstract:The incidences of tendinopathies have been increasing worldwide in recent years, causing huge economic burdens and mental stress in patients and reducing the quality of human life to varying degrees. Animal models are important tools in tendinopathy research and play a crucial role in the study of pathophysiological changes and novel treatment modalities. This article reviews the status of animal models developed in recent years and discusses the advantages and disadvantages of several common modeling protocols, including the choice of modeling animal and modeling site and the alterations to injured tendons, with the aim of providing a reference to help future researchers select suitable and efficient animal models.

Abstract:Mouse models are of great interest for studying human respiratory pathogens. However, evolutionary species divergence has led to differences in lung structure and the immune system between humans and mice, making the study of human respiratory pathogens in mouse models a longstanding challenge. In contrast, mice with a humanized immune system can faithfully reproduce human immune responses to respiratory pathogen infection, and mice with humanized lung and lung-immune systems can be used to examine human trophic respiratory pathogen infection and the corresponding immune responses. This review summarizes the contributions and recent progress of these types of humanized mice in respiratory pathogen research.

Abstract:Eurodegenerative diseases are refractory diseases that can cause symptoms such as loss of sensation, loss of motor function and memory failure. Although traditional treatment method can delay the progress of such diseases, they have obvious limitations. A potential new treatment method involving neural stem cell transplantation can effectively promote the functional recovery and tissue regeneration of nerve cells, and provides a promising treatment for neurodegenerative diseases. Therefore, this paper reviews the existing sources of neural stem cells and research progress using these cells in the treatment of neurodegenerative diseases, and provides the foundation and direction for further research and application of neural stem cell transplantation in neurodegenerative diseases.

Abstract:Functional dyspepsia (FD) is a common and recurring disease, which is difficult to treat so it becomes a refractory disease. Because of the unknown etiology of FD, the current modeling method used in animal research remain controversial. The lasting effect of animal models provides an important reference value for potential treatments of FD. However, no article has comprehensively summarized the lasting effect of existing animal models of FD. To provide a reliable reference for establishing an FD animal model, we classify each model as sustained type and temporary type based on its lasting effect.

Abstract:High altitude pulmonary oedema ( HAPE) is defined as acute respiratory failure following hypoxic exposure to high altitude. The pathogenesis is not clear, and there is no standard animal model. Animal models is the basis of exploring the pathogenesis and treatment on HAPE. Also, it’ s the basis of searching for effective diagnosis and treatment. The method of production of animal models include singly hypoxia exposure, hypoxia exposure combined with fatigue, transgenic technology, etc. This brief review focuses on the animal models from the model creation and model evaluation, in order to provide useful information for researchers and medical practitioners.